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Biomedical subjects

D S Young

Publications and source records attributed to D S Young.

At least 19 recordsLinked to original sources

How do somersaulters land on their feet?

Body movements of trampolinists landing upright from forward somersaults, with eyes open and closed, were analyzed to test a theory of how braking and timing of actions are conjointly controlled. In regulating landing, rotation has to be slowed by extending the body so that it reaches the upright just as the feet hit the trampoline. Extending a theory of visual control of linear braking, it was hypothesized that upright landing is achieved by perceptually regulating body extension so as to keep the ratio angle of body to upright: rate of change of angle (the tau function of the angle) proportional to time-to-landing. The data support the hypothesis, indicate that vision improves precision of control, and argue further for the value of the tau function in the perceptual regulation of action.

Attention

Two-dimensional electrophoresis of urine specimens from patients with renal disease.

In an effort to develop non-invasive markers capable of characterizing renal disease with greater sensitivity and specificity than those currently available, urinary proteins were studied by high-resolution two-dimensional electrophoresis in order to catalog those proteins which appeared to be most affected by a variety of renal diseases. Urine specimens were prepared by high-pressure liquid chromatography and subjected to two-dimensional gel electrophoresis. Proteins were visualized with silver stain. Gels from 17 patients were analyzed in detail and compared to standard maps of human urinary proteins and plasma. The two-dimensional gels displayed approximately 100 times the number of proteins demonstrated by high resolution agarose electrophoresis. We have identified 34 proteins whose urinary concentrations were most affected by renal disease. Twenty seven were of plasma origin, based upon comigration with plasma samples (17 of unknown identity and function). Seven proteins were observed in normal urine but not present in plasma. These proteins, which may represent kidney tissue proteins, were not apparent in the urine of patients with proteinuria, most likely due to dilutional effects.

Biomarkers

Pharmacodynamics and pharmacokinetics of cyclosporin A in the newborn pig.

The disposition kinetics of cyclosporin A in the neonates as well as age-related differences in lymphocyte responses to cyclosporin A are unknown. A single intravenous infusion of cyclosporin A was given to neonatal (2.5 or 5 mg/kg) and mature pigs (10 mg/kg) and blood cyclosporin A levels were measured by RIA. The neonates had longer elimination half-life and lower drug clearance than mature animals. Suppression in lymphocyte proliferation was only observed in mixed lymphocyte reaction and phytohemagglutinin-stimulated cultures of the 2-hour samples from neonates receiving 5 mg/kg. We conclude that neonatal pig exhibit different cyclosporin A pharmacokinetics and show higher sensitivity to cyclosporin A than mature animals.

Aging

Determination and validation of reference intervals.

A brief overview of the concept of the reference interval and its application in medical practice is presented. The populations from whom it is possible to derive reference intervals are discussed. Procedures used to develop reference intervals from both a selected healthy population and from hospitalized patients are discussed, and the influence of statistical method on presented reference intervals is reviewed. However, the weakness of using a reference interval derived from a population of individuals to facilitate interpretation of test results is illustrated in relationship to the variability of test results within an individual. In spite of the efforts that are made within the clinical laboratory through development of reference intervals to provide maximum guidance to clinicians to facilitate their proper interpretation of test values in patients, it is apparent that much of the carefully derived scientific information is ignored in actual practice.

Data Interpretation, Statistical

SI units for clinical laboratory data.

The international System of Units (SI) has not yet been accepted by American physicians because of reluctance to convert to a new system and the corresponding need for relearning. The impetus to introduce the SI came from European laboratory scientists; the system was later accepted (not always enthusiastically) by physicians after the same objections now voiced by their US counterparts were overcome. Now that many American laboratory scientists are actively studying and assessing the benefits of SI, we may have begun the chain of events that will lead to general acceptance by physicians in the United States.

Abbreviations as Topic

Automated monitoring of drug-test interactions.

A computer-based file of the effects of drugs on clinical laboratory tests was used in a university hospital to generate reports of all potential interactions between the drugs administered to a patient and the laboratory tests ordered on his body fluids. More than 13,000 patient days were monitored in four different nursing units. The physician users of the system indicated that automatic reporting of possible drug-test interactions had both educational and clinical value. A critical review of patient charts suggested that automatic reporting of drug-test interactions caused physicians to alter therapy in about 0.1% of instances in which a report was generated. The users themselves indicated that they altered treatment as a result of the reports in a substantially greater number of cases.

Attitude of Health Personnel

Variance components of serum constituents in healthy individuals.

Analytical, intra-individual, and inter-individual components of variance were estimated in 10 volunteers for 34 assays encompassing 22 different constituents. Replicate blood specimens were obtained four times weekly. Nine constituents were measured with more than one instrument [Technicon AutoAnalyzer II and SMAC System, Perkin-Elmer Kinetic Enzyme Analyzer KA-150, and (or) the Abbott Bichromatic Aanalyzer ABA-100]. For those constituents that were stored for randomized batch analysis, results were examined for evidence of changes during storage and within-run analytical drift. Alkaline phosphatase, cholesterol, dopamine-beta-hydroxylase, and SMAC-measured lactate dehydrogenase had a ratio of intra-individual to interindividual variance of less than 0.10, thus exhibiting a high individuality. This ratio was greater than one for sodium, carbon dioxide, and creatine kinase. Analytical variance was more than 30% of total variance for sodium, carbon dioxide, calcium, total protein, and chloride. Analytical variance was less than 20% of intra-individual variance for bilirubin, creatine kinase, KA-150-measured lactate dehydrogenase, triglycerides, and urea nitrogen. Limits for the expected difference between measurements of the same constituent for the same individual on different days are also presented.

Adult

Analytical interferences of drugs in clinical chemistry.

The effects of several drugs were tested on analytical methods used in the clinical laboratory to measure the concentration of certain chemical constituents and activity of enzymes in body fluids. Drugs were studied initially at reported toxic concentrations, but if they had an effect at this level effects of lower concentrations were also investigated. The drugs were first studied on the methods of the Technicon SMACTM analyzer. Subsequently, methods in use with the Du Pont ACA and Technicon AutoAnalyzerTM I or II were evaluated. The most commonly affected method was the phosphotungstate reduction procedure for measuring uric acid. However, methods for measuring total protein and albumin were also affected frequently, as were determinations of alkaline phosphatase and lactate dehydrogenase activity.

Chemistry, Clinical

Prospective applications of calorimetry in the clinical laboratory.

Calorimetric analysis depends on the direct proportionality between the heat changes that occur during chemical reactions and the amount of reacting substances. Potential uses of calorimetry in the clinical laboratory are discussed, with examples. The calorimetric technique does not require optically clear specimens, and if the specificity of the measured reaction is assured, calorimetry can be used for quantitative determinations of components that are present in a complex matrix system such as body fluids. Specific enzymic reactions have been used to measure substrates and enzyme activities in biological specimens calorimetrically, with precision, sensitivity, and accuracy comparable to routine photometric techniques. The application of calorimetry in the clinical laboratory is limited now by its slowness, but development of automated instruments may enable the technique to become competitive with conventional analytical techniques in the clinical laboratory.

Calorimetry

Enzyme kinetics in single cells: concept and model.

We describe a technique whereby it is possible to measure enzyme activity in a singel cell. The model chosen involved the measurement of myeloperoxidase activity in a polymorphonuclear neutrophil leukocyte. Details of the apparatus are described. The experiments necessary to optimize the reaction conditions are summarized. The nature of the phases of the reaction are described. The technique appears to have further application in measurement of the activities of other enzymes in leukocytes or other cells.

Densitometry

Anticonvulsants in serum, determined with a fully mechanized enzyme analyzer.

The "EMIT" enzyme immunoassay system (Syva) that involves use of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) as the enzyme label has been adapted to a fully mechanized kinetic enzyme analyzer for analysis of phenobarbital, phenytoin, and primidone. This procedure, compared with the gas-chromatographic procedure of Kupferberg [Clin. Chim. Acta 29, 283 (1970)], gave a weighted regression line--forced through the origin--of y=(1.01+/-0.04) x for phenobarbital, y=(0.95+/-0.04) x for primidone. Within-run coefficients of variation based on single determinations were 9,11, and 22% for primidone, phenobarbital, and phenytoin, respectively. Run-to-run assay CV was 6% for primidone and phenobarbital and 13% for phenytoin, based on the means of triplicate determinations of a sample with a mid-range concentration.

Evaluation Studies as Topic

Calorimetric enzymic measurement of uric acid in serum.

Uric acid in serum was determined calorimetrically with a batch type microcalorimeter, by measuring the heat evolved during a coupled uricase/catalase enzymic reaction in tris(hydroxymethyl)aminomethane HCl buffer (pH 9.0 at 30 degrees C). Heat evolution and concentration are linearly related through the physiological range of serum uric acid concentrations and the method is free of interferences of the sort encountered with spectrophotometric methods. Precision and accuracy are good (CV, 2%) and the results correlate well with those obtained by a mechanized colorimetric uricase/peroxidase system.

Calorimetry